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Lauren E Cain, Ellen C Caniglia, Andrew Phillips, Ashley Olson, Roberto Muga, Santiago Pérez-Hoyos, Sophie Abgrall, Dominique Costagliola, Rafael Rubio, Inma Jarrín, Heiner Bucher, Jan Fehr, Ard van Sighem, Peter Reiss, François Dabis, Marie-Anne Vandenhende, Roger Logan, James Robins, Jonathan A C Sterne, Amy Justice, Janet Tate, Giota Touloumi, Vasilis Paparizos, Anna Esteve, Jordi Casabona, Rémonie Seng, Laurence Meyer, Sophie Jose, Caroline Sabin, Miguel A Hernán
OBJECTIVE: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. METHODS: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen...
October 2016: Medicine (Baltimore)
Santiago Avila-Ríos, Claudia García-Morales, Margarita Matías-Florentino, Daniela Tapia-Trejo, Bismarck F Hernández-Álvarez, Sumaya E Moreira-López, Carlos J Quant-Durán, Guillermo Porras-Cortés, Gustavo Reyes-Terán
BACKGROUND: Increasing HIV pre-treatment drug resistance (PDR) levels have been observed in regions with increasing antiretroviral treatment (ART) coverage. However, data is lacking for several low/middle-income countries. We present the first PDR survey in Nicaragua since ART introduction in the country in 2003. METHODS: HIV-infected, ART-naïve Nicaraguan individuals were enrolled at Roberto Calderón Hospital, the largest national HIV referral center, from 2011 to 2015...
2016: PloS One
K Steegen, M Bronze, M A Papathanasopoulos, G van Zyl, D Goedhals, E Variava, W MacLeod, I Sanne, W S Stevens, S Carmona
BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL...
September 22, 2016: Journal of Antimicrobial Chemotherapy
Santosh K Karade, Manisha V Ghate, Devidas N Chaturbhuj, Dileep B Kadam, Subramanian Shankar, Nitin Gaikwad, Shraddha Gurav, Rajneesh Joshi, Suvarna S Sane, Smita S Kulkarni, Swarali N Kurle, Ramesh S Paranjape, Bharat B Rewari, Raman R Gangakhedkar
The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs).In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ± 2 months of ART initiation...
September 2016: Medicine (Baltimore)
Katia Falasca, Marcella Reale, Claudio Ucciferri, Marta Di Nicola, Giuseppe Di Martino, Chiara D'Angelo, Simona Coladonato, Jacopo Vecchiet
The HIV may trigger a process of neuronal loss and axonal degeneration throughout the brain, which is carried on by the immune system releasing of proinflammatory cytokines, so that chronic inflammation associated with dysregulated innate immune response, glial cell dysfunction, and adverse antiretroviral therapy (ART) effect play an important role causing milder HIV-associated neurocognitive disorders or asymptomatic neurocognitive impairment. All patients have been tested for neurocognitive functioning through a comprehensive, five-domain neuropsychological battery performed in the study...
October 12, 2016: AIDS Research and Human Retroviruses
Martina Kovarova, Uma Shanmugasundaram, Caroline E Baker, Rae Ann Spagnuolo, Chandrav De, Christopher C Nixon, Angela Wahl, J Victor Garcia
BACKGROUND: Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers highlight that HIV acquisition is a major health concern for women and children globally. They also emphasize the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed. METHODS: 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with low cytotoxicity, was administered orally to NOD/SCID/γc(-/-) mice and to bone marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection...
August 1, 2016: Journal of Antimicrobial Chemotherapy
Mauro Zaccarelli, Maria Mercedes Santoro, Daniele Armenia, Vanni Borghi, William Gennari, Caterina Gori, Federica Forbici, Ada Bertoli, Lavinia Fabeni, Alberto Giannetti, Stefania Cicalini, Rita Bellagamba, Massimo Andreoni, Claudio Maria Mastroianni, Cristina Mussini, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Andrea Antinori
BACKGROUND: Beyond the detection of resistant HIV strains found in plasma samples, archival HIV-DNA in peripheral blood mononuclear cells (PBMCs) might represent a reservoir of additional resistance. OBJECTIVE: To characterize the HIV-1 resistance in PBMCs from patients with suppressed or low-level viremia (50-1000 copies/mL) and evaluate its added value compared to the resistance detected in previous plasma genotypic resistance tests (GRTs). STUDY DESIGN: HIV-1 infected patients selected for treatment change despite low/undetectable viremia were tested...
September 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Maximilian Donath, Timo Wolf, Martin Stürmer, Eva Herrmann, Markus Bickel, Pavel Khaykin, Siri Göpel, Peter Gute, Annette Haberl, Philipp de Leuw, Gundolf Schüttfort, Annemarie Berger, Christoph Stephan
There are concerns about central nervous system (CNS)-replication of HIV-1 in patients on boosted protease inhibitors. Purpose of this study was to compare HIV-1 viral loads (VLs) from patients treated with only boosted dual protease inhibitor (bdPI), versus combination antiretroviral therapy (cART group), containing two nucleoside analogue reverse transcriptase inhibitors (NRTI) and a third partner. All patients from a large German HIV-treatment cohort with available medication, clinical and demographic data, including results from simultaneous HIV-1 viral load (VL) assessments in cerebrospinal fluid (CSF) and blood plasma, were retrospectively evaluated as controlled cross-sectional study...
July 28, 2016: Medical Microbiology and Immunology
Sathasivam Sivamalar, Thongadi Ramesh Dinesha, Selvamurthi Gomathi, Ambrose Pradeep, Jayaseelan Boobalan, Sunil S Solomon, Selvamuthu Poongulali, Suniti Solomon, Balakrishnan Pachamuthu, Shanmugam Saravanan
Lack of HIV-1 viral load monitoring in resource-limited settings leads to development of HIV drug resistance mutations, although WHO recommends viral load testing for monitoring as this helps in preserving future treatment options and also avoid unnecessary switching to more expensive drugs. A total of 101 patients attaining first-line treatment failure (FTF) were followed till second-line treatment failure (STF) to study the rate of accumulation of TAMs, their future drug options, and genetic evolution. The result shows predominant NRTI mutations was M184V/I (87...
July 26, 2016: AIDS Research and Human Retroviruses
Emanuele Focà, Massimiliano Fabbiani, Mattia Prosperi, Eugenia Quiros Roldan, Francesco Castelli, Franco Maggiolo, Elisa Di Filippo, Simona Di Giambenedetto, Roberta Gagliardini, Annalisa Saracino, Massimo Di Pietro, Andrea Gori, Laura Sighinolfi, Angelo Pan, Maria Concetta Postorino, Carlo Torti
INTRODUCTION: Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) suffer from faster progression of liver fibrosis (LF) and have greater risk of worse clinical outcomes. We evaluated predictors and incidence of these events in a large multicentre cohort. METHODS: We selected all HIV-infected patients starting a first-line combination antiretroviral therapy (cART), with detectable HCV-RNA, without exposure to interferon/ribavirin, with ≥2 fibrosis-4 index (FIB-4) classifications before cART...
July 2016: Medicine (Baltimore)
Uma Shanmugasundaram, Martina Kovarova, Phong T Ho, Nathaniel Schramm, Angela Wahl, Michael A Parniak, J Victor Garcia
BACKGROUND: The nucleoside reverse transcriptase inhibitor (NRTI) 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) in preclinical development exhibits improved safety and antiviral activity profiles with minimal drug resistance compared to approved NRTIs. However, the systemic antiviral efficacy of EFdA has not been fully evaluated. In this study, we utilized bone marrow/liver/thymus (BLT) humanized mice to investigate the systemic effect of EFdA treatment on HIV replication and CD4+ T cell depletion in the peripheral blood (PB) and tissues...
2016: PloS One
Camille Bernaud, Lydie Khatchatourian, Audrey Rodallec, Nolwenn Hall, Philippe Perre, Marine Morrier, Solène Pineau, Thomas Jovelin, Elisabeth André-Garnier, François Raffi, Clotilde Allavena
BACKGROUND: Tenofovir DF/FTC/rilpivirine (TDF/FTC/RPV) is a single tablet regimen considered as safe and efficacious in HIV population as long as food requirements, concomitant PPI administration, and compromised antiviral activity have been carefully reviewed. We evaluated TDF/FTC/RPV in a real-life setting with focus on clinical and virological outcomes. METHODS: OCEAN II is a prospective, two-centre observational study. From September 2012 to December 2013, antiretroviral-naive patients with HIV RNA <100,000 copies/mL or wishing to switch for simplification were considered for TDF/FTC/RPV...
October 2016: Infectious Diseases
E Rouveix, E Mortier, A Beauchet, C Dupont, J Gerbe, V Daneluzzi, P Brazille, H Berthe, D Zucman, P Genet, A-M Simonpoli, P de Truchis
OBJECTIVE: Several therapeutic combination antiretroviral therapy regimen are available for initial treatment in naïve HIV infected patients. The choice of a particular regimen remains often subjective. The aim of this study was to determine factors associated with the choice of molecules in initial ARV prescriptions. METHODS: From 01/01 to 30/10/2014, every initial cART prescription was analyzed regarding patients and physicians characteristics. Then, prescriptions were evaluated by an independent committee of ART prescribers...
June 29, 2016: La Revue de Médecine Interne
Hamed Naziri, Kazem Baesi, Abdolvahab Moradi, Mohammad R Aghasadeghi, Alijan Tabarraei, Willi McFarland, Mohamad Ali Davarpanah
Resistance to antiretroviral agents is a significant concern in the clinical management of HIV-infected individuals, particularly in areas of the world where treatment options are limited. In this study, we aimed to identify HIV drug-resistance-associated mutations in 40 drug-naïve patients and 62 patients under antiretroviral therapy (ART) referred to the Shiraz HIV/AIDS Research Center - the first such data available for the south of Iran. HIV reverse transcriptase and protease genes were amplified and sequenced to determine subtypes and antiretroviral- resistance-associated mutations (RAMs)...
September 2016: Archives of Virology
Santiago Avila-Rios, Omar Sued, Soo-Yon Rhee, Robert W Shafer, Gustavo Reyes-Teran, Giovanni Ravasi
BACKGROUND: HIV transmitted drug resistance (TDR) remains at moderate level in Latin America and the Caribbean (LAC). However, different epidemiologic scenarios could influence national and sub-regional TDR levels and trends. METHODS AND FINDINGS: We performed a systematic review of currently available publications on TDR in antiretroviral treatment-naïve adults in LAC. Ninety-eight studies published between January 2000 and June 2015 were included according to critical appraisal criteria and classified by sub-region: Brazil (50), Mesoamerica (17), Southern Cone (16), Andean (8) and Caribbean (7)...
2016: PloS One
Thongadi Ramesh Dinesha, Selvamurthi Gomathi, Jayaseelan Boobalan, Sathasivam Sivamalar, Sunil S Solomon, Ambrose Pradeep, Selvamuthu Poongulali, Suniti Solomon, Balakrishnan Pachamuthu, Shanmugam Saravanan
According to 2013 WHO guidelines, Tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. 167 HIV-1 infected patients attaining immunological failure after TDF based first-line HAART were included in the study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database was used for mutation interpretation. REGA V3.0 was used of HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184V (59.9%), K65R (28.1%), TAMs (29...
June 22, 2016: AIDS Research and Human Retroviruses
Willem-Martin Gerber, David Meyer, Derrick P Smit
PURPOSE: The ocular penetration of systemically administered antiretroviral drugs (ARVs), which is important in the clinical setting of HIV uveitis, is unknown. This study aimed to assess the ocular penetration of different antiretroviral drugs in an animal model. METHODS: Twenty-five male New Zealand white rabbits were assigned to one of five treatment groups. Each group received a single oral dose of an antiretroviral drug (lamivudine, tenofovir, efavirenz, lopinavir, and raltegravir)...
September 2016: Journal of Ocular Pharmacology and Therapeutics
Alberto M La Rosa, Linda J Harrison, Babafemi Taiwo, Carole L Wallis, Lu Zheng, Peter Kim, Nagalingeswaran Kumarasamy, Mina C Hosseinipour, Bernadette Jarocki, John W Mellors, Ann C Collier
BACKGROUND: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings. METHODS: A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe)...
June 2016: Lancet HIV
M D Sanna, D Peroni, T Mello, C Ghelardini, A Quattrone, N Galeotti
Nucleoside reverse transcriptase inhibitors (NRTIs) are key components of HIV/AIDS treatment to reduce viral load. However, antiretroviral toxic neuropathy has become a common peripheral neuropathy among HIV/AIDS patients leading to discontinuation of antiretroviral therapy, for which the underlying pathogenesis is uncertain. This study examines the role of neurofilament (NF) proteins in the spinal dorsal horn, DRG and sciatic nerve after NRTI neurotoxicity in mice treated with zalcitabine (2',3'-dideoxycitidine; ddC)...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Oluwafeyisetan Adebiyi, Olubunmi Adebiyi, Peter Owira
BACKGROUND: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development of nucleoside reverse transcriptase inhibitors (NRTIs)-induced mitochondrial toxicities. Available options in managing these complications have, so far, produced controversial results, thus necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging effects of naringin, a plant-derived flavonoid, have previously been demonstrated...
May 20, 2016: Current HIV Research
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